1293 Underrecognized Severe Sleep-Disordered Breathing in Pituitary-Dependent Cushing’s Disease: A Bidirectional Challenge

Abstract Introduction Cushing’s syndrome, defined by chronic hypercortisolism, is associated with an increased prevalence of obstructive sleep apnea (OSA). Cushing’s disease, caused by ACTH-secreting pituitary adenomas, represents a specific subset of this disorder. Although OSA is increasingly recognized in hypercortisolemic states, detailed descriptions of severe OSA in Cushing’s disease remain limited. We present a case in which the diagnosis of severe OSA was delayed until after endocrine evaluation and surgical management. Report of case(s) A 40-year-old female with type 2 diabetes and hyperlipidemia was evaluated for progressive weight gain and worsening glycemic control. She reported a 100-pound weight gain over five years despite sustained lifestyle efforts. Physical examination revealed nuchal and supraclavicular fat pads and purple striae, prompting evaluation for Cushing's disease. Laboratory studies confirmed hypercortisolism, and pituitary MRI identified a macroadenoma invading the right cavernous sinus. She underwent endoscopic transsphenoidal resection, but hypercortisolism persisted postoperatively with residual tumor noted. During this period, she endorsed symptoms of OSA, including loud snoring, witnessed apneas, morning headaches, dry mouth, impaired concentration, and daytime fatigue. Home sleep apnea testing performed after her endocrine work-up confirmed severe OSA, with an apnea-hypopnea index of 98.3 events per hour and an oxygen saturation nadir of 51%. Although obesity and altered fat distribution are established contributors to OSA, the severity of sleep-disordered breathing appeared disproportionate to her anthropometric profile. Features of hypercortisolism, such as central fat deposition and dorsocervical fat accumulation, likely intensified upper airway obstruction, consistent with evidence that elevated cortisol independently correlates with increased OSA risk. Conclusion Population-based data show that Cushing's syndrome confers a 2.82-fold increased risk of OSA independent of weight. Conversely, severe untreated OSA can produce a pseudo-Cushing's biochemical pattern, and one case series has demonstrated biochemical improvement in hypercortisolism after CPAP therapy. This bidirectional relationship complicates diagnostic interpretation. This case highlights that OSA in pituitary-dependent Cushing's disease can be extremely severe and may go underrecognized during initial endocrine evaluation. Clinicians should maintain a low threshold for sleep assessment in hypercortisolemic patients and consider incorporating screening into the pre-operative work-up. Early identification and treatment may improve cardiometabolic outcomes and quality of life. Support (if any)